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Tumours ferment glucose to lactate even in the presence of oxygen (aerobic glycolysis; Warburg effect). The pentose phosphate pathway (PPP) allows glucose conversion to ribose for nucleic acid synthesis and glucose degradation to lactate. The nonoxidative part of the PPP is controlled by transketolase enzyme reactions. We have detected upregulation of a mutated transketolase transcript (TKTL1) in human malignancies, whereas transketolase (TKT) and transketolase-like-2 (TKTL2) transcripts were not upregulated. Strong TKTL1 protein expression was correlated to invasive colon and urothelial tumours and to poor patients outcome. TKTL1 encodes a transketolase with unusual enzymatic properties, which are likely to be caused by the internal deletion of conserved residues. We propose that TKTL1 upregulation in tumours leads to enhanced, oxygen-independent glucose usage and a lactatebased matrix degradation. As inhibition of transketolase enzyme reactions suppresses tumour growth and metastasis, TKTL1 could be the relevant target for novel anti-transketolase cancer therapies. We suggest an individualised cancer therapy based on the determination of metabolic changes in tumours that might enable the targeted inhibition of invasion and metastasis.

Abstract. Except for hereditary disease, genetic factors that contribute to the development of renal epithelial tumors are unknown. There is a possibility that the MDR1 encoded plasma membrane transporter P-glycoprotein (PGP) influences the risk of development of renal neoplasms. PGP is known to be involved in uptake, binding, transport, and distribution of xenobiotics. There is evidence that the MDR1 C3435T polymorphism drives expression and modulates disease risk. In an explorational case-control study, constitutional genotype frequencies were established at MDR1 C3435T of 537 healthy control subjects and compared with those of 212 patients with renal epithelial tumors. There were 179 clear cell renal cell carcinoma (CCRCC) and 33 tumors collectively assigned as non-CCRCC. In a second study, genotypes of another 150 healthy control subjects and 50 patients with three non-CCRCC types (26 papillary RCC, 11 chromophobe RCC, and 13 renal oncocytic adenoma) were compared. PCR-restriction fragment length polymorphism-based analysis of constitutional DNA, and statistical analysis were applied. PGP expression was analyzed by quantitative immunohistochemistry. The explorational study showed a significant association between T allele frequency and the occurrence of tumors (P ϭ 0.007). When tumors were histopathologically distinguished into frequent CCRCC and less frequent non-CCRCC, both patient groups contributed to this effect with a seemingly strong influence by the latter (P ϭ 0.0419). The second study established the T allele as a risk factor especially for non-CCRCC (P ϭ 0.0005) with the highest risk for homozygote TT allele carriers (P Ͻ 0.0001). Independently, MDR1C3435T genotype associated variations in PGP expression were shown in normal renal parenchyma with a 1.5-fold difference of median values (TT, 1.9; CC, 2.8; P ϭ 0.0065). The data provide evidence for PGP to influence the susceptibility to develop renal epithelial tumors by virtue of its MDR1 C3435T polymorphism and changes in expression. Especially T and TT carriers are at risk for developing non-CCRCC, i.e., papillary and chromophobe RCC as well as oncocytic adenomas.Renal epithelial tumors contribute approximately 3% to the overall cancer incidence and mortality. Renal cell carcinomas (RCC) compose clear cell RCC (CCRCC) in 75% to 80%, papillary (chromophilic) RCC in 10%, and chromophobe RCC in 5%. Others include granular cell carcinoma, spindle cell carcinoma, and duct Bellini and unclassified carcinomas (1). There are also benign oncocytic and papillary adenomas, which account for approximately 5% of all renal epithelial neoplasms. Although the molecular origins of these histologic subentities have been identified, i.e., mutations and hypermethylations of the VHL and RASSF1A tumor suppressor genes in CCRCC (2-5), mutations of the MET proto-oncogene in papillary RCC (6,7), and loci for hereditary chromophobe RCC and oncocytic adenoma on chromosome 17p11.2 (8), their cause and interindividual differences in susceptibility remain elusive.It is interes...

OBJECTIVE To report our experience with over 300 patients treated with percutaneous nephrolithotomy (PNL), for although PNL was established as a treatment in the 1970s, its use diminished with the introduction of extracorporeal shockwave lithotripsy (ESWL); clinical experience with ESWL showed its limitations, and the role of PNL for treating urolithiasis was redefined, which with improvements in instruments and lithotripsy technology has expanded the capability of percutaneous stone disintegration. PATIENTS AND METHODS The study included 315 patients (156 males, 159 females, aged 13–85 years) treated with PNL in our department between 1987 and 2002. The mean (range) stone diameter was 27 (7–52) mm. The kidney was punctured under ultrasonography guidance via a lower‐pole calyx whenever possible. The working channel was dilated using an Alken dilator under X‐ray control. If necessary, a flexible renoscope was used. Ultrasonic, pneumatic and laser probes were used for lithotripsy. RESULTS Four weeks after treatment the total stone‐free rate was 96.5%; 45.7% of all patients were primarily stone‐free, 21.3% had clinically insignificant residual stones that passed spontaneously within 4 weeks after PNL, and 33% of the patients needed auxiliary measures (a second PNL, ESWL, ureterorenoscopy). Overall, the early complication rate was 50.8%, the most common complications being transient fever (27.6%), clinically insignificant bleeding (7.6%) or both (3.2%); 3.5% of the patients developed urinary tract infections (with no signs of urosepsis), 3.2% had renal colic and 2.9% upper urinary tract obstruction. One patient (0.3%) developed acute pancreatitis after PNL; one died from urosepsis and one needed selective angiographic embolization of the punctured kidney due to bleeding. No patient required transfusions and there were no injuries to neighbouring organs. CONCLUSIONS These results show that PNL causes no significant blood loss or major complications in almost all patients. Two aspects may especially reduce the potential complications: ultrasonography‐guided renal puncture and using PNL in an experienced centre. PNL is a highly efficient procedure that provides fast and safe stone removal.

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After experience with more than 200 cases of retroperitoneoscopy the access technique has been significantly simplified. The procedure is standardized, safe and reproducible.